Burkholderia pseudomallei, a motile, Gram-negative, environmental saprotroph, is an emerging infectious disease problem and a previously-weaponinzed CDC Tier 1 select agent. It causes melioidosis in humans, which, in its acute form, can be fatal within days if untreated. Although endemic to southeast Asia and northern Australia, there is evidence that B. pseudomallei is spreading beyond established boundaries. Lack of a vaccine and lack of rapid diagnostic tests, together with the bacterium's low infectious dose and intrinsic antibiotic resistance, underscore the need to develop new therapeutics and new strategies for eliminating B. pseudomallei from contaminated environments, the only reservoir from which transmission to humans occurs. Contact-Dependent Growth Inhibition (CDI) is a phenomenon in which bacteria use the toxic C-terminus of a large surface-exposed exoprotein to inhibit the growth of neighboring bacteria upon cell-cell contact. If present in the cytoplasm, immunity proteins bind to the toxic polypeptides, blocking their catalytic activity and preventing cell death. The toxic C-termini of CDI system exoproteins and the immunity proteins are polymorphic and immunity proteins protect against CDI in an allele-specific manner. It has been suggested that this polymorphism allows bacteria to use CDI systems to discriminate self from non-self as a mechanism for kin selection in microbiological communities, but this hypothesis has not been tested. Whether there is a hierarchy of potencies of different CDI systems and whether the possession of multiple CDI systems is advantageous have also not been tested. We propose experiments to determine if bcpAIOB genes in B. pseudomallei do, as predicted, encode proteins that mediate interbacterial competition and biofilm formation in B. pseudomallei. We will determine if different bcpAIOB alleles encode proteins with different potencies, and if possession of multiple alleles confers a competitive advantage. We will also determine if inter-species CDI occurs and if Burkholderia thailandensis, a non-pathogen that lives in the same ecological niche as B. pseudomallei, can be engineered to produce multiple CDI systems and if this strain can out-compete B. pseudomallei and prevent or destroy B. pseudomallei biofilms. Our results will form the foundation for the exploitation of CDI systems for use as decontaminants and, potentially, therapeutics.

Public Health Relevance

Burkholderia pseudomallei, the bacterium that causes melioidosis, is both an emerging infectious disease problem and a potential biothreat agent. We will determine how B. pseudomallei uses BcpAIOB proteins for interbacterial Contact-Dependent Growth Inhibition (CDI) and biofilm formation. We will also determine the feasibility of constructing a non-pathogenic strain that produces multiple CDI systems simultaneously for use as a decontaminant and a therapeutic.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IDM-B (80))
Program Officer
Mukhopadhyay, Suman
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
Zip Code
Perault, Andrew I; Cotter, Peggy A (2018) Three distinct contact-dependent growth inhibition systems mediate interbacterial competition by the cystic fibrosis pathogen Burkholderia dolosa. J Bacteriol :
Danka, Elizabeth S; Garcia, Erin C; Cotter, Peggy A (2017) Are CDI Systems Multicolored, Facultative, Helping Greenbeards? Trends Microbiol 25:391-401
Garcia, Erin C; Perault, Andrew I; Marlatt, Sara A et al. (2016) Interbacterial signaling via Burkholderia contact-dependent growth inhibition system proteins. Proc Natl Acad Sci U S A 113:8296-301
Garcia, Erin C; Cotter, Peggy A (2016) Burkholderia thailandensis: Growth and Laboratory Maintenance. Curr Protoc Microbiol 42:4C.1.1-7